1,2-Dichloroethane → HCID 58066259, compound

HRID 2410601Notes

Reaction equation

HRID 2410601 reaction equation
[OH:1][N:2]=[C:3]([C:5]1[CH:21]=[CH:20][C:8]([CH2:9][N:10]([CH3:19])[CH2:11][C:12]([O:14]C(C)(C)C)=[O:13])=[C:7]([C:22]([F:25])([F:24])[F:23])[CH:6]=1)[NH2:4].[CH3:26][O:27][CH2:28][C:29]1[CH:34]=[C:33]([C:35](O)=O)[CH:32]=[CH:31][C:30]=1[C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][C:39]=1[CH3:44].C(Cl)CCl>CC#N.N1C=CC=CC=1>[CH3:26][O:27][CH2:28][C:29]1[CH:34]=[C:33]([C:35]2[O:1][N:2]=[C:3]([C:5]3[CH:21]=[CH:20][C:8]([CH2:9][N:10]([CH3:19])[CH2:11][C:12]([OH:14])=[O:13])=[C:7]([C:22]([F:24])([F:23])[F:25])[CH:6]=3)[N:4]=2)[CH:32]=[CH:31][C:30]=1[C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][C:39]=1[CH3:44]

Participants

6

Reactant 3

HCID 111,2-DichloroethaneHCID 594958222-(Methoxymethyl)-2'-methylbiphenyl-4-carboxylic acidHCID 76685370HCID 76685370, compound

Product 1

HCID 58066259HCID 58066259, compound

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6342AcetonitrileSolvent

Procedure

To a solution of Intermediate 74 (0.112 g, 0.31 mmol) and Intermediate 3 (0.067 mg, 0.26 mmol) in MeCN (2 mL) was added EDC (0.069 g, 0.36 mmol). The reaction mixture was stirred at room temperature for 18 hours. The reaction mixture was diluted with pyridine (2 mL) and heated at 150° C. in the microwave for 30 minutes. The reaction was repeated and combined to work up. The solvent was removed in vacuo and the residue dissolved in DCM. The mixture was washed with water and the organic phase passed through a hydrophobic frit. The solvent was evaporated in vacuo. The residue was purified by SCX chromatography. The material was treated with a 4N solution of HCl in dioxane (4 mL) and the resulting mixture was stirred at 70° C. for 18 hours. The solvent was evaporated in vacuo and the residue purified by preparative HPLC, affording the title compound as an orange oil. 1H NMR (CDCl3, 400 MHz) δ 8.98 (1H, br s), 8.50 (1H, s), 8.43-8.34 (2H, m), 8.14 (2H, d, J=8.0 Hz), 7.34-7.21 (4H, m), 7.12 (1H, d, J=7.4 Hz), 4.26-4.18 (4H, m), 3.56 (2H, s), 3.32 (3H, s), 2.62 (3H, s), 2.07 (3H, s). LC/MS (Method A): 526 (M+H)+. HPLC (Method F) Rt 3.74 min (Purity: 99.4%).

Workup

  1. temperatureheated at 150° C. in the microwave for 30 minutes
  2. customThe solvent was removed in vacuo
  3. dissolutionthe residue dissolved in DCM
  4. washThe mixture was washed with water
  5. customThe solvent was evaporated in vacuo
  6. customThe residue was purified by SCX chromatography
  7. additionThe material was treated with a 4N solution of HCl in dioxane (4 mL)
  8. stirringthe resulting mixture was stirred at 70° C. for 18 hours
  9. customThe solvent was evaporated in vacuo
  10. customthe residue purified by preparative HPLC

Sources & evidence

ORD record
ord-9f17c8d58a2345a98a7eec7a9b5f4ad4
Source dataset
uspto-grants-2014_08
Patent number
US08815919B2

Reaction notes

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